About

Xin Gao, PhD, is an Assistant Professor who obtained her PhD from the University of Wisconsin-Madison in 2016, working in Emery Bresnick’s lab. Following her doctoral studies, she completed two postdoctoral fellowships: one at Albert Einstein College of Medicine in Paul Frenette's lab, and another at UW-Madison in Jing Zhang's lab. Dr. Gao has been recognized with a K01 award and the ASH Fellow-to-Faculty Scholar Award, which have supported her research focusing on the bone marrow microenvironment and hematopoietic stem cells. She joined the faculty at UW-Madison in 2023.

Research topics

• Biology
• Immunology
• Cancer research
• Genetics
• Cell biology

Selected publications

• Shared immune-inflammatory mechanisms between ulcerative colitis and periodontitis: a multi-omics analysis

  Frontiers in Immunology · 2025-08-27 · 3 citations

  articleOpen accessSenior authorCorresponding

  Background Ulcerative colitis (UC) and periodontitis (PD) are chronic inflammatory diseases with increasing evidence of bidirectional communication through the oral–gut axis. However, the immunological mechanisms underlying their co-occurrence remain largely unclear. Methods We conducted a bidirectional Mendelian randomization (MR) analysis to evaluate potential causal relationships between UC and PD. Transcriptomic data from public repositories were integrated to identify shared differentially expressed genes. Immune-related genes were further screened using three machine learning approaches. Enrichment analysis and immune cell infiltration profiling were performed to explore underlying mechanisms. A rat model combining UC and PD was established to validate key findings in vivo . Results MR analysis revealed a unidirectional causal effect of UC on PD. Among the intersected immune-related genes, CXCL6 was identified as a hub gene significantly upregulated in both UC and PD. It was associated with neutrophil infiltration and pathways related to chemokine signaling and mucosal barrier disruption. In a dual-disease rat model, CXCL6 expression was further elevated in colonic tissues compared to UC alone, aligning with aggravated epithelial damage. Conclusion Our study identifies a shared immune signature between UC and PD, highlighting CXCL6 as a pivotal mediator. These insights deepen understanding of oral–gut mucosal interactions and inform future biomarker and mechanistic studies.

  PublisherOA PDFDOI

• Predicting Lung Cancer EGFR Mutation Status via Integration of Deep Learning and Radiomics in Pulmonary CT Imaging

  Advances in transdisciplinary engineering · 2025-06-04

  book-chapterOpen access

  In the spectrum of mortality cases attributed to malignancies, lung cancer holds a prominent position. Mutations in the epidermal growth factor receptor (EGFR) are crucial in both the development and therapy of non-small cell lung cancer (NSCLC). Traditional methods, like tissue biopsy, tend to be invasive. This research explores the application of deep learning and radiomics for the non-invasive prediction of EGFR mutation status in patients with NSCLC, utilizing pulmonary computed tomography (CT) images. This investigation encompassed 135 patients with NSCLC. Radiomic features were obtained from the regions of tumors. Meanwhile, a convolutional neural network (CNN) was employed to extract high-level features from the CT images. The predictive model was developed by integrating both feature sets and evaluated on internal and external test sets using accuracy, sensitivity, specificity, and area under the curve (AUC). The model achieved AUCs of 0.844 (95% CI: 0.562–1.000) in internal validation and 0.724 (95% CI: 0.598–0.845) in external validation. These results demonstrate that deep learning, in combination with radiomics, can effectively predict the status of EGFR mutation, offering a promising non-invasive alternative to traditional biopsy-based methods.

  PublisherOA PDFDOI

• Type I Interferon Pathway Activation Disrupts Monocyte Maturation and Enhances Immune Evasion in Multiple Myeloma

  Advanced Science · 2025-11-30

  articleOpen access

  Monocyte-derived cells, including osteoclasts, dendritic cells, and macrophages, are key components of the immunosuppressive tumor microenvironment in multiple myeloma (MM). However, the mechanisms linking monocyte dysfunction to immune evasion remain incompletely understood. In this study, single-cell RNA sequencing (scRNA-seq) of peripheral blood (PB) and bone marrow (BM) monocytes was performed from healthy donors (HDs) and MM patients to generate a comprehensive single-cell transcriptional map. Although PB and BM monocytes displayed comparable cellular compositions, MM monocytes exhibited marked transcriptional alterations, most prominently within the type I interferon (IFN) signaling pathway. Trajectory analyses revealed IFN-driven disruptions in monocyte differentiation and developmental trajectories in both PB and BM compartments. Functional co-culture assays demonstrated that activation of the type I IFN pathway enhanced MM cell proliferation, suggesting that IFN-mediated monocyte reprogramming facilitates tumor progression. In an independent validation cohort, longitudinal sampling before and after induction therapy confirmed that anti-myeloma treatment alleviated the excessive IFN response of BM monocytes. Collectively, these findings uncover a mechanistic link between aberrant IFN activation and monocyte dysregulation in MM, providing new insights into immune dysfunction and highlighting the IFN pathway as a potential therapeutic target to restore anti-tumor immunity.

  PublisherOA PDFDOI

• The mRNA export pathway licenses viral mimicry response and antitumor immunity by actively exporting nuclear retroelement transcripts

  Science Translational Medicine · 2025-04-09 · 2 citations

  articleCorresponding

  Nuclear retroelement transcripts (RTs), which can be elicited both transcriptionally and posttranscriptionally, form double-stranded RNA (dsRNA) in cytosol to trigger the viral mimicry response (VMR) and antitumor immunity. However, the strength of the induced VMR varies tremendously across tumor types, and the underlying mechanisms remain poorly understood. Here, we demonstrate that the mRNA export pathway modulates the VMR through actively exporting nuclear RTs for cytosolic dsRNA formation after their induction. Tumor cells hijack this process for immune evasion through aberrant coactivator-associated arginine methyltransferase 1 (CARM1) expression. Mechanistically, we show that the cytoplasmic transportation of RTs by the mRNA export pathway is counteracted by the RNA exosome, which cleaves multiple transcripts within this pathway, including those encoding the essential DExD-box helicase 39A (DDX39A) and the adaptor protein ALYREF. CARM1 enhances the RNA exosome activity to attenuate the nuclear export of RTs by the mRNA export pathway through two synergistic mechanisms: (i) transcriptionally activating several RNA exosome components and (ii) posttranslationally methylating arginine 6 of the RNA exosome subunit EXOSC1, which protects it from proteasome-mediated degradation. Collectively, our study highlights the critical active regulatory role of the mRNA export pathway in transporting nuclear RTs into the cytosol for triggering the VMR and tumor immunity. Furthermore, we propose that enhancing the mRNA export pathway activity, either through CARM1 inhibition or RNA exosome modulation, could reinforce the therapeutic agent-induced VMR, thus holding the promise for overcoming tumor immune evasion and immunotherapy resistance.

  PublisherDOI

• The role of metagenomic next-generation sequencing in diagnosing and managing post-kidney transplantation infections

  Frontiers in Cellular and Infection Microbiology · 2025-01-07 · 4 citations

  reviewOpen access

  Kidney transplantation (KT) is a life-saving treatment for patients with end-stage renal disease, but post-transplant infections remain one of the most significant challenges. These infections, caused by a variety of pathogens, can lead to prolonged hospitalization, graft dysfunction, and even mortality, particularly in immunocompromised patients. Traditional diagnostic methods often fail to identify the causative organisms in a timely manner, leading to delays in treatment and poorer patient outcomes. This review explores the application of metagenomic next-generation sequencing (mNGS) in the diagnosis of post-KT infections. mNGS allows for the rapid, comprehensive detection of a wide range of pathogens, including bacteria, viruses, fungi, and parasites, without the need for culture-based techniques. We discuss the advantages of mNGS in early and accurate pathogen identification, its role in improving patient management, and the potential challenges in its clinical implementation. Additionally, we consider the future prospects of mNGS in overcoming current diagnostic limitations and its potential for guiding targeted therapies, particularly in detecting antimicrobial resistance and emerging pathogens. This review emphasizes the promise of mNGS as an essential tool in improving the diagnosis and treatment of infections in KT recipients.

  PublisherDOI

• USP39 at the crossroads of cancer immunity: regulating immune evasion and immunotherapy response through RNA splicing and ubiquitin signaling

  Frontiers in Immunology · 2025-09-08 · 2 citations

  reviewOpen access

  Deubiquitinating enzymes (DUBs) are responsible for the removal of ubiquitin from substrates, thereby antagonizing ubiquitination and regulating a multitude of biological pathways including cell cycle progression, signal transduction, and transcriptional regulation. Ubiquitin Specific Protease-39 (USP39), a pivotal member of the ubiquitin-specific protease family, is intricately linked to innumerable pathophysiological processes. In this review, we first provide an overview of the specific structural domains and biological functions of USP39, with a particular focus on its role in DNA damage repair and RNA splicing processes. Then, we delineate the function of USP39 in maintaining epithelial morphology, resistance to viral infection, vascular remodeling, and pathological states. Moreover, we particularly focus on the aberrant expression of USP39 in various cancers and its effect on cancer markers, as well as on the regulatory role of USP39 in tumor progression. In conclusion, a comprehensive analysis of the structural domains and functional properties of USP39, a detailed investigation into its interaction mechanisms with diverse substrates, and the accelerated development of related inhibitors will provide a novel theoretical foundation for the treatment of numerous diseases, including tumors. Importantly, targeting USP39 may overcome resistance to checkpoint inhibitors, offering a promising approach to enhance cancer immunotherapy efficacy.

  PublisherOA PDFDOI

• Discovery of a highly specific radiolabeled antibody targeting B-cell maturation antigen: Applications in PET imaging of multiple myeloma

  European Journal of Nuclear Medicine and Molecular Imaging · 2024-09-11 · 6 citations

  article
  PublisherDOI

• High temporal resolution prediction of mortality risk for single AML patient via deep learning

  iScience · 2024-07-06 · 2 citations

  articleOpen accessSenior authorCorresponding

  Acute myeloid leukemia (AML) is highly heterogeneous, necessitating personalized prognosis prediction and treatment strategies. Many of the current patient classifications are based on molecular features. Here, we classified the primary AML patients by predicted death risk curves and investigated the survival-directly-related molecular features. We developed a deep learning model to predict 5-year continuous-time survival probabilities for each patient and converted them to death risk curves. This method captured disease progression dynamics with high temporal resolution and identified seven patient groups with distinct risk peak timing. Based on clusters of death risk curves, we identified two robust AML prognostic biomarkers and discovered a subgroup within the European LeukemiaNet (ELN) 2017 Favorable category with an extremely poor prognosis. Additionally, we developed a web tool, De novo AML Prognostic Prediction (DAPP), for individualized prognosis prediction and expression perturbation simulation. This study utilized deep learning-based continuous-time risk modeling coupled with clustering-predicted risk distributions, facilitating dissecting time-specific molecular features of disease progression.

  PublisherDOI

• Gene expression prognostic of early relapse risk in low‐risk B‐cell acute lymphoblastic leukaemia in children

  eJHaem · 2024-03-15 · 4 citations

  articleOpen access

  Abstract ETV6 :: RUNX1 is the most common fusion gene in childhood acute lymphoblastic leukaemia (ALL) and is associated with favorable outcomes, especially in low‐risk children. However, as many as 10% of children relapse within 3 years, and such early relapses have poor survival. Identifying children at risk for early relapse is an important challenge. We interrogated data from 87 children with low‐risk ETV6 :: RUNX1 ‐positive B‐cell ALL and with available preserved bone marrow samples (discovery cohort). We profiled somatic point mutations in a panel of 559 genes and genome‐wide transcriptome and single‐nucleotide variants. We found high TIMD4 expression (> 85th‐percentile value) at diagnosis was the most important independent prognostic factor of early relapse (hazard ratio [HR] = 5.07 [1.76, 14.62]; p = 0.03). In an independent validation cohort of low‐risk ETV6 :: RUNX1 ‐positive B‐cell ALL ( N = 68) high TIMD4 expression at diagnosis had an HR = 4.78 [1.07, 21.36] ( p = 0.04) for early relapse. In another validation cohort including 78 children with low‐risk ETV6 :: RUNX1 ‐negative B‐cell ALL, high TIMD4 expression at diagnosis had an HR = 3.93 [1.31, 11.79] ( p = 0.01). Our results suggest high TIMD4 expression at diagnosis in low‐risk B‐cell ALL in children might be associated with high risk for early relapse.

  PublisherOA PDFDOI

• Safety and Feasibility of Internal Fixation Using Bioabsorbable Versus Titanium Materials for Short‐Level Lamina Reimplantation: A Comparative Clinical Study

  Orthopaedic Surgery · 2024-11-04 · 1 citations

  articleOpen access

  OBJECTIVE: Lamina-implantation is gradually becoming the main surgical method for the treatment of intraspinal tumors. Traditional titanium (Ti) internal fixation not only produces artifacts, which affects the observation of tumors and dural sac closure, but also faces the problem of secondary surgical removal. In this study, absorbable material were used in lamina replantation for the first time and was evaluated for its efficacy and safety. METHODS: We retrospectively enrolled patients who underwent short-segment lamina replantation for intraspinal tumors in our center from February 2020 to November 2022. After condition matching of the number of fixation segment and fixation position, the baseline information, complications, neurological function, quality of life, spinal mobility and bone healing rate of the absorbable group and the Ti group were compared. Fisher exact, Chi-square, or rank sum test were used for categorical variables, and t-test was used for continuous variables to distinguish differences between groups. RESULTS: Cerebrospinal fluid leak was the most common complication, with no difference between the two groups (12.9% vs. 19.4%, p = 0.366). The bone healing rates of the two groups at 3 months after surgery were 77.4% and 87.1%, respectively, and there was no significant difference (p = 0.508). At 1 year after surgery, the resorbable group showedlower levels of anxiety/depression (1.20 ± 0.41 vs. 1.61 ± 0.61, p = 0.050), however, it did not affect the overall quality of life of the patients at 1 year. CONCLUSION: Both titanium and absorbable internal fixation have shown good clinical results in the treatment of intraspinal tumors by laminareplantation. Regardless of cost, absorbable screws and plates are also suitable options for patients undergoing lamina replantation, because it has no stress shielding effect and does not require secondary removal. In addition, there are no artifacts in the image, which is more conducive to observing the recurrence of the tumor and the closure of the dural sac.

  PublisherOA PDFDOI

Frequent coauthors

• Shaoshan Hu

  Harbin Medical University

  61 shared

• Hang Ji

  Sichuan University

  56 shared

• Emery H. Bresnick

  University of Wisconsin Carbone Cancer Center

  53 shared

• Jiheng Zhang

  Harbin Medical University

  46 shared

• Jianyang Du

  Zhejiang Provincial People's Hospital

  46 shared

• Kirby D. Johnson

  University of Wisconsin Carbone Cancer Center

  45 shared

• Zhihui Liu

  Liaoning Provincial People's Hospital

  45 shared

• Nan Wang

  Minzu University of China

  42 shared

Labs

• Gao LabPI